Oral care compositions

ABSTRACT

An oral care composition comprising (i) basic amino acid in free or salt form, (ii) calcium carbonate, (iii) a fluoride ion source, (iv) a flavoring agent comprising less than 50% menthol, and (v) an anionic surfactant, wherein the anionic surfactant is present in an amount from 1.00 weight % to 1.39 weight % is provided.

BACKGROUND

This invention relates to oral care compositions comprising a basicamino acid or salt together with calcium carbonate and a fluoride ionsource, and to methods of using and of making these compositions.

Arginine and other basic amino acids have been proposed for use in oralcare and are believed to have significant benefits in combating cavityformation and tooth sensitivity. It is also desirable to include theminerals fluoride and calcium in oral care compositions for their oralcare benefits. Oral care compositions should be stable and maintainintegrity when stored for a significant period of time.

Accordingly, there is a need for a stable oral care product comprising abasic amino acid, fluoride and calcium.

BRIEF SUMMARY

Although it is desirable to reduce the flavoring amount in dentifriceformulations for certain demographics such as children, the presentinventors found that reduction in flavoring agent compromised theintegrity of the final product. Further, attempts to improve thisintegrity with higher surfactant levels did not address the problem andin some instances increased the oil/water phase separation. However,when the surfactant level was lowered it was surprisingly found thatstability increased. In turn, it has surprisingly been discovered thatthe combination of 1.00 weight % to 1.39 weight % anionic surfactanttogether with a basic amino acid, calcium carbonate, a flavoring agentcomprising less than 50% menthol and a fluoride ion source provides ahighly stable oral care formulation that can deliver excellent oral carebenefits.

According to a first aspect of the invention there is provided an oralcare composition comprising

-   -   (i) a basic amino acid in free or salt form,    -   (ii) calcium carbonate,    -   (iii) a fluoride ion source,    -   (iv) a flavoring agent comprising less than 50% menthol, and    -   (v) an anionic surfactant,        wherein the anionic surfactant is present in an amount from 1.00        weight % to 1.39 weight %.

Optionally the oral care composition comprises a bacteriostaticpreservative. Further optionally the oral care composition comprisesbenzyl alcohol. Further optionally the oral care composition comprises0.25 weight % to 0.75 weight % benzyl alcohol. Further optionally theoral care composition comprises 0.45 weight % to 0.55 weight % benzylalcohol.

Optionally the calcium carbonate is precipitated calcium carbonate.Further optionally the oral care composition comprises from 20 weight %to 60 weight % calcium carbonate. Further optionally the oral carecomposition comprises from 38 weight % to 44 weight % calcium carbonate.Further optionally the oral care composition comprises from 40 weight %to 43 weight % calcium carbonate.

Optionally the anionic surfactant is a water-soluble salt of a C₁₀ toC₁₈ alkyl sulfate. Further optionally the anionic surfactant is sodiumlauryl sulfate. Further optionally the oral care composition comprises1.05 weight % to 1.30 weight % sodium lauryl sulfate. Further optionallythe oral care composition comprises 1.10 weight % to 1.25 weight %sodium lauryl sulfate. Further optionally the oral care compositioncomprises 1.14 weight % sodium lauryl sulfate.

Optionally the composition further comprises a flavoring agent.Optionally the composition comprises 0.1 weight % to 2.0% flavoringagent. Further optionally the composition comprises 0.25 weight % to1.1% flavoring agent. Further optionally the oral care compositioncomprises 0.50 weight % flavoring agent. Optionally, the flavoring agentcomprises menthol, carvone and/or anethole. Further optionally, theflavoring agent comprises oils of peppermint and spearmint. Optionally,the flavoring agent comprises less than 50% menthol, preferably lessthan 45% menthol, preferably less than 42% menthol.

Optionally the composition comprises a fluoride ion source selected fromone or more of stannous fluoride, sodium fluoride, potassium fluoride,sodium monofluorophosphate, sodium fluorosilicate, ammoniumfluorosilicate, amine fluoride, ammonium fluoride and combinations ofone or more thereof. Further optionally the fluoride ion sourcecomprises sodium monofluorophosphate. Further optionally the oral carecomposition comprises 0.90 weight % to 1.30 weight % sodiummonofluorophosphate. Further optionally the oral care compositioncomprises 1.1 weight % sodium monofluorophosphate.

Optionally the composition comprises a basic amino acid selected fromone or more of arginine, lysine, histidine, citrulline, ornithine,creatine, diaminobutanoic acid, diaminoproprionic acid, and salts andcombinations thereof. Further optionally the oral care compositioncomprises a basic amino acid selected from arginine, citrulline,ornithine and salts thereof. Further optionally the oral carecomposition comprises L-arginine or a salt thereof. Further optionallythe oral care composition comprises 1.0 weight % to 5.0 weight % of abasic amino acid or salt thereof. Further optionally the compositioncomprises 1.5 weight % to 3.5 weight % L-arginine bicarbonate.

Optionally the composition comprises

-   -   (i) 1.0 to 5.0 weight % of a basic amino acid in free or salt        form    -   (ii) 38 weight % to 44 weight % precipitated calcium carbonate    -   (iii) 0.90 weight % to 1.30 weight % sodium monofluorophosphate.    -   (iv) 0.25 weight % to 1.0% flavoring agent comprising less than        50% menthol    -   (v) 1.05 weight % to 1.3 weight % sodium lauryl sulfate.

Optionally the composition comprises

-   -   (i) 1.0 to 5.0 weight % of a basic amino acid in free or salt        form    -   (ii) 38 weight % to 44 weight % precipitated calcium carbonate    -   (iii) 0.90 weight % to 1.30 weight % sodium monofluorophosphate    -   (iv) 0.25 weight % to 1.0% flavoring agent comprising less than        50% menthol    -   (v) 1.05 weight % to 1.3 weight % sodium lauryl sulfate    -   (vi) 0.65 weight % to 1.00 weight % sodium        carboxymethylcellulose.

Optionally the oral care composition is a dentifrice. Further optionallythe composition is a toothpaste or gel.

According to a further aspect of the invention there is provided amethod to

-   -   (i) reduce or inhibit formation of dental caries,    -   (ii) reduce, repair or inhibit pre-carious lesions of the        enamel,    -   (iii) reduce or inhibit demineralization and promote        remineralization of the teeth,    -   (iv) reduce hypersensitivity of the teeth,    -   (v) reduce or inhibit gingivitis,    -   (vi) promote healing of sores or cuts in the oral cavity,    -   (vii) reduce levels of acid producing bacteria,    -   (viii) increase relative levels of arginolytic bacteria,    -   (ix) reduce or inhibit microbial biofilm formation in the oral        cavity,    -   (x) reduce or inhibit plaque formation in the oral cavity,    -   (xi) promote systemic health,    -   (xii) clean teeth and oral cavity        comprising applying an effective amount of an oral care        composition as herein described to the oral cavity of a subject        in need thereof. Optionally the subject is a mammal. Further        optionally the subject is a juvenile.

According to a further aspect of the invention there is provided an oralcare composition as herein described for use in a method to

-   -   (i) reduce or inhibit formation of dental caries,    -   (ii) reduce, repair or inhibit pre-carious lesions of the        enamel,    -   (iii) reduce or inhibit demineralization and promote        remineralization of the teeth,    -   (iv) reduce hypersensitivity of the teeth,    -   (v) reduce or inhibit gingivitis,    -   (vi) promote healing of sores or cuts in the oral cavity,    -   (vii) reduce levels of acid producing bacteria,    -   (viii) increase relative levels of arginolytic bacteria,    -   (ix) reduce or inhibit microbial biofilm formation in the oral        cavity,    -   (x) reduce or inhibit plaque formation in the oral cavity,    -   (xi) promote systemic health,    -   (xii) clean teeth and oral cavity.

According to a further aspect of the invention there is provided use ofan oral care composition as herein described to

-   -   (i) reduce or inhibit formation of dental caries,    -   (ii) reduce, repair or inhibit pre-carious lesions of the        enamel,    -   (iii) reduce or inhibit demineralization and promote        remineralization of the teeth        in a subject in need thereof. Optionally the subject is a        mammal. Further optionally the subject is a juvenile.

According to a further aspect of the invention there is provided amethod for preparing an oral care composition as herein describedcomprising the sequential steps of

-   -   a. adding the basic amino acid to a solution comprising the        fluoride ion source,    -   b. adding the calcium carbonate, and    -   c. adding the anionic surfactant.

Further areas of applicability of the present invention will becomeapparent from the detailed description provided hereinafter. It shouldbe understood that the detailed description and specific examples, whileindicating the preferred embodiment of the invention, are intended forpurposes of illustration only and are not intended to limit the scope ofthe invention.

The composition may include a first feature described in one exampleherein, as well as a second feature described in another example herein.In other words, the invention contemplates mixing and matching featuresfrom the disclosed embodiments in various combinations.

DETAILED DESCRIPTION

The following description of the preferred embodiment(s) is merelyexemplary in nature and is in no way intended to limit the invention,its application, or uses.

As used throughout, ranges are used as shorthand for describing each andevery value that is within the range. Any value within the range can beselected as the terminus of the range. In addition, all references citedherein are hereby incorporated by referenced in their entireties. In theevent of a conflict in a definition in the present disclosure and thatof a cited reference, the present disclosure controls.

Unless otherwise specified, all percentages and amounts expressed hereinand elsewhere in the specification should be understood to refer topercentages by weight. The amounts given are based on the active weightof the material.

It has surprisingly been found that formulating an oral care compositioncomprising a basic amino acid, calcium ions and fluoride ions with 1.00weight % to 1.39 weight % anionic surfactant results in a stablecomposition with excellent shelf life.

The oral care compositions of the present invention comprise a basicamino acid in free or salt form. The basic amino acids which can be usedin the compositions and methods of the invention include not onlynaturally occurring basic amino acids such as arginine, lysine andhistidine, but also any basic amino acids having a carboxyl group and amamino group in the molecule which are water-soluble and provide anaqueous solution with a pH of about 7 or greater. For example, basicamino acids may include but are not limited to arginine, lysine,citrulline, ornithine, creatine, histidine, diaminobutanoic acid,diamino proprionic acid, salts thereof and combinations thereof. Incertain embodiments the basic amino acid may comprise arginine,citrulline, ornithine and salts and combinations thereof. In certainembodiments the basic amino acid comprises arginine, for exampleL-arginine.

The basic amino acid may be in free or salt form. In certainembodiments, the basic amino acid is in salt form. Such salts should bepharmaceutically acceptable. In certain embodiments the basic amino acidis a salt derived from a pharmaceutically acceptable inorganic ororganic acid or base, for example an acid addition salt formed by anacid which forms a physiologically acceptable anion, for examplehydrochloride or bromide, or a base addition salt formed by a base whichforms a physiologically acceptable cation such as an alkali metal oralkaline earth metal, for example potassium, sodium, calcium ormagnesium. In certain embodiments the basic amino acid is a bicarbonatesalt of an amino acid. For example, the basic amino acid may be argininebicarbonate. In certain embodiments the basic amino acid is L-argininebicarbonate.

In certain embodiments the basic amino acid in free or salt form ispresent in an amount from 0.5 weight % to 5.0 weight % based on thetotal weight of the composition. In certain embodiments the basic aminois present in an amount of from 0.5 weight % to 3.0 weight %, from 1.0weight % to 2.5 weight % or from 1.2 weight % to 2.0 weight %. Incertain embodiments the basic amino acid is present in an amount of 1.5weight %. In certain embodiments the basic amino acid in salt form ispresent in an amount of from 1.0 weight % to 4.0 weight %, from 1.5weight % to 3.5 weight %, from 2.0 weight % to 3.5 weight % or from 2.0weight % to 3.0 weight %. In certain embodiments the basic amino acid insalt form is present in an amount of about 2.7 weight %.

In certain embodiments the composition comprises from 0.5 weight % to5.0 weight % arginine, for example 1.0 weight % to 4.0 weight %arginine, 1.0 weight % to 2.0 weight % or about 1.5 weight % arginine.In certain embodiments the composition comprises L- or D-arginine infree or salt form. In certain embodiments the composition comprisesL-arginine in free or salt form.

In certain embodiments the composition comprises arginine bicarbonate inan amount from 1.0 weight % to 5.0 weight % based on the total weight ofthe composition. In certain embodiments the arginine bicarbonate ispresent in an amount of from 1.5 weight % to 4.0 weight %, from 1.5weight % to 3.5 weight %, from 2.0 weight % to 3.5 weight % or from 2.0weight % to 3.0 weight %. In certain embodiments the argininebicarbonate is present in an amount of about 2.7 weight %. In certainembodiments the composition comprises L-arginine bicarbonate.

The compositions of the invention comprise calcium carbonate. Naturalcalcium carbonate is found in rocks such as chalk, limestone, marble andtravertine, as well as egg shells and mollusk shells. Natural calciumcarbonate can be used as an abrasive in oral care compositions.Typically, natural calcium carbonate abrasive is finely ground limestonewhich may optionally be refined or partially refined to removeimpurities. In certain embodiments, the natural calcium carbonate has anaverage particle size of less than 10 microns, for example 3 to 7microns or about 5.5. microns.

In certain embodiments the composition comprises precipitated calciumcarbonate. Precipitated calcium carbonate (PCC) is generally made bycalcining limestone to make oxide (lime) which can then be convertedback to calcium carbonate by reaction with carbon dioxide in water.Precipitated calcium carbonate has a different crystal structure fromnatural calcium carbonate. It is generally more friable and more porous,thus having lower abrasivity and higher water absorption. In certainembodiments, the calcium carbonate comprises precipitated calciumcarbonate with an average particle size of 1 to 5 microns and forexample no more than 0.1% or preferably 0.05% by weight of particleswhich would not pass through a 325 mesh. In certain embodiments, the PCCparticles have a D₉₀ of 3 to 10 microns, for example about 3.4 to about9.0 microns (Sedigraph). In certain embodiments the PCC particles have aD₉₀ of about 4.3 microns. In certain embodiments the PCC particles havea D₅₀ of 1 to 7 microns, for example about 1.5 to about 4.0 microns(Sedigraph). In certain embodiments the PCC particles have a D₅₀ ofabout 2.4 microns. In certain embodiments the PCC particles have a D10of about 0.3 to about 1.30 microns (Sedigraph), for example a D₁₀ of 1to 2 microns. In certain embodiments the PCC particles have a D10 ofabout 1.3 microns. In certain embodiments the PCC particles have a D₅₀by Sedigraph of 1.87 to 1.93 microns and a D₉₀ by Sedigraph of 3.45 to3.55 microns. In certain embodiments the PCC particles have particlesize by Malvern of D₁₀ 1.10-1.70, D₅₀ 5.00-7.00 and D₉₀ 10.50-14.50microns. In certain embodiments the PCC particles have particle size bySedigraph of D₁₀ 0.3-1.30, D₅₀ 2.50-4.00 and D₉₀ 6.00-9.00 microns. Incertain embodiments the PCC particles have particle sizes by BeckmanCoulter of D₁₀ 0.22-0.49, D₅₀ 4.10-5.90 and D₉₀ 9.70-12.90 microns. Incertain embodiments the PCC particles have particle size by Malvern ofD₁₀ 0.60-1.20, D₅₀ 3.50-6.00 and D₉₀ 7.00-12.00 microns. In certainembodiments the PCC particles have particle size by Cilag of D₁₀0.30-0.90, D₅₀ 3.00-5.00 and D₉₀ 5.50-8.50 microns. In certainembodiments the PCC particles have particle size by Beckman Coulter ofD₁₀ 0.15-0.22, D₅₀ 2.80-4.20 and D₉₀ 5.00-9.70 microns. In certainembodiments the PCC particles have a high water absorption. In certainembodiments the PCC particles have a water absorption of 15-70 g/100 g,for example 15 to 26 g/100 g or 17 to 20 g/100 g.

In certain embodiments the composition comprises additionalcalcium-containing abrasives, for example a calcium phosphate abrasivesuch as tricalcium phosphate, hydroxyapatite or dicalcium phosphatedehydrate. In certain embodiments the composition comprises silicaabrasives such as precipitated silicas having a mean particle size of upto about 20 μm, sodium metaphosphate, potassium metaphosphate, aluminiumsilicate, calcined alumina, bentonite or other siliceous materialsand/or combinations thereof.

In certain embodiments, the composition comprises from 20 to 60 weight %calcium carbonate, for example from 30 to 50 weight %, from 35 to 45weight % or from 38 to 44 weight %. In certain embodiments thecomposition comprises from 40 to 43 weight %, for example from 41 to 42weight %.

In certain embodiments, the composition comprises from 40 to 43 weight %precipitated calcium carbonate.

The compositions of the present invention comprises a fluoride ionsource. In certain embodiments, the composition comprises one or morefluoride ion sources, for example soluble fluoride salts. In certainembodiments the composition comprises a fluoride ion source selectedfrom one or more of stannous fluoride, sodium fluoride, potassiumfluoride, sodium monofluorophosphate, sodium fluorosilicate, ammoniumfluorosilicate, amine fluoride, ammonium fluoride and combinations ofone or more thereof.

In certain embodiments, the composition comprises sodiummonofluorophosphate.

In certain embodiments, the composition comprises a fluoride ion sourcein an amount sufficient to supply about 25 ppm to about 25,000 ppmfluoride ions, for example from about 500 ppm to about 200 ppm, fromabout 1000 ppm to about 1600 ppm.

The weight of fluoride salt may be selected in order to provide theappropriate level of fluoride ion in the formulation. In certainembodiments the composition comprises about 0.01 weight % to about 10weight % fluoride ion source, for example about 0.03 to about 5.0 weight%, or about 0.1 to about 1.0 weight %.

In certain embodiments the composition comprises about 0.03 to about 5.0weight % sodium monofluorophosphate, for example about 0.5 to about 2.0weight %, from 0.90 to about 1.30 weight % or from about 1.80 to about1.30 weight % sodium monofluorophosphate.

The compositions of the invention comprise 1.00 to 1.39 weight % anionicsurfactant. It has surprisingly been discovered that this level ofanionic surfactant stabilizes formulations comprising a basic aminoacid, calcium carbonate and fluoride.

In certain embodiments, the composition comprises an anionic surfactantthat comprises a water-soluble salt of a C₁₀ to C₁₈ alkyl sulfate. Incertain embodiments, the composition comprises one or more surfactantselected from sodium lauryl sulfate, sodium lauroyl sarcosinate andsodium coconut monoglyceride sulfonates. In certain embodiments thecomposition comprises a mixture of one or more anionic surfactants.

In certain embodiments, the composition comprises from 1.00 to 1.30weight % anionic surfactant, for example from 1.05 to 1.25 weight %,from 1.15 to 1.25 weight % or about 1.20 weight % anionic surfactant. Incertain embodiments, the composition comprises from 1.05 to 1.25 weight%, from 1.15 to 1.25 weight % or about 1.20 weight % sodium laurylsulfate. In certain embodiments the composition comprises 95% sodiumlauryl sulfate in an amount of from 1.05 weight % to 1.30 weight %, from1.10 weight % to 1.25 weight % or about 1.14 weight %.

In certain embodiments the compositions of the present inventioncomprise a flavoring agent. The flavoring agent may comprise one or moreessential oils as well as various flavoring aldehydes, esters and/oralcohols. In certain embodiments, the flavoring agent comprises one ormore essential oil selected from oils of peppermint, wintergreen,sassafras, clove, sage, eucalyptus, marjoram, cinnamon, lemon, lime,grapefruit and orange. In certain embodiments, the flavoring agentcomprises menthol, carvone and/or anethole. In certain embodiments, theflavoring agent comprises oils of peppermint and spearmint. In certainembodiments, the flavoring agent comprises less than 50% menthol,preferably less than 45% menthol, preferably less than 42% menthol.

In certain embodiments the composition comprises 0.1 to 2.0 weight %,0.25 to 1.5 weight %, 0.25 weight % to 1.1 weight %, 0.30 weight % to0.8 weight %, 0.40 weight % to 0.60 weight % or about 0.50 weight %flavoring agent. In certain embodiments the composition comprises aflavoring agent in an amount acceptable to juveniles. In certainembodiments the composition comprises a flavoring agent in an amountthat is lower than that provided in an adult formulation in order toprovide a gentler flavor to the consumer.

In certain embodiments, the composition comprises a bacteriostaticpreservative. In certain embodiments, the composition comprises benzylalcohol. In certain embodiments the composition comprises 0.25 weight %to 0.75 weight %, 0.35 weight % to 0.60 weight % or 0.40 weight % to0.60 weight % bacteriostatic preservative. In certain embodiments thecomposition comprises 0.25 weight % to 0.75 weight %, 0.35 weight % to0.60 weight % or 0.40 weight % to 0.60 weight % benzyl alcohol. Incertain embodiments the composition comprises about 0.50 weight % benzylalcohol. In certain embodiments the composition comprises more than 0.30weight % benzyl alcohol as preservative in order to increase themicrorobustness of the composition.

In certain embodiments the composition comprises a reduced amount offlavoring agent and an increased amount of bacteriostatic preservative.In certain embodiments the composition comprises more than 0.30 weight %preservative and no more than 0.8 weight % flavoring agent. In certainembodiments the composition comprises 0.4 weight % to 0.6 weight %benzyl alcohol and 0.3 weight % to 0.7 weight % flavoring agent.

In certain embodiments the composition comprises 1.0 to 5.0 weight % ofa basic amino acid in free or salt form, 38 weight % to 44 weight %precipitated calcium carbonate, 0.90 weight % to 1.30 weight % sodiummonofluorophosphate, 0.25 weight % to 1.0% flavoring agent and 1.10weight % to 1.30 weight % sodium lauryl sulfate. In certain embodimentsthe composition comprises 1.0 to 5.0 weight % of a basic amino acid infree or salt form, 38 weight % to 44 weight % precipitated calciumcarbonate, 0.90 weight % to 1.30 weight % sodium monofluorophosphate,0.25 weight % to 1.0% flavoring agent, 1.10 weight % to 1.30 weight %sodium lauryl sulfate and 0.35 weight % to 0.60 weight % benzyl alcohol.

In certain embodiments the composition is a toothpaste, transparentpaste, or gel. In certain embodiments the composition is a dentifricesuch as a toothpaste or gel.

In certain embodiments the composition may comprise one or morechelating agents. In certain embodiments the composition comprises oneor more chelating agent able to complex calcium found in the cell wallsof bacteria. In certain embodiments the composition comprises one ormore soluble pyrophosphate as chelating agent. In certain embodimentsthe pyrophosphate salts can be any of the alkali metal pyrophosphatesalts. In certain embodiments the salts include tetra alkali metalpyrophosphate, dialkali metal diacid pyrophosphate, trialkali metalmonoacid pyrophosphate and mixtures thereof wherein the alkali metalsare sodium or potassium. In certain embodiments the compositioncomprises such pyrophosphate salts in an amount to provide at leastabout 1 weight % pyrophosphate ions, for example about 1.5 weight % toabout 6 weight % or about 3.5 weight % to about 6 weight %.

In certain embodiments the compositions of the invention include one ormore polymers such as polyethylene glycols, polyvinylmethyl ether maleicacid copolymers and polysaccharides (e.g. cellulose derivatives such ascarboxymethyl cellulose or microcrystalline cellulose, or polysaccharidegums such as xanthan gum or carrageenan gum). Acidic polymers, forexample polyacrylate gels, may be provided as free acids or partially orfully neutralized water soluble alkali metal (e.g. potassium and sodium)or ammonium salts.

In certain embodiments the composition comprises about 0.05 to about 5%of an agent which enhances the delivery and retention of oral careagents to and retention thereof on oral surfaces. In certain embodimentsthe composition comprises synthetic anionic polymeric polycarboxylatessuch 1:4 to 4:1 copolymers of maleic anhydride or acid with anotherpolymerizable ethylenically unsaturated monomer, preferably methyl vinylether/maleic anhydride having a molecular weight of about 30,000 toabout 1,000,000. In certain embodiments the composition comprises fromabout 0.05 to about 3% by weight of such agents. In certain embodimentsthe composition comprises a thickening material to enhance theperformance of the formulation. In certain embodiments the thickeningagents are carboxyvinyl polymers, carrageenan, hydroxyethyl celluloseand water soluble salts of cellulose ethers such as sodium carboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose.Natural gums such as karaya, gum arabic and gum tragacanth may also beincluded. In certain embodiments the composition comprises colloidalmagnesium aluminium silicate or finely divided silica. In certainembodiments a thickening agent is present in an amount of about 0.5 toabout 5.0%. In certain embodiments the composition comprises from about0.5 to about 5% cellulose gum.

In certain embodiments the composition comprises from 1.00 to 1.30weight % anionic surfactant together with 0.5 weight % to 1.5 weight %sodium carboxymethyl cellulose. In certain embodiments, the compositioncomprises from 1.05 to 1.25 weight %, sodium lauryl sulfate and 0.65weight % to 1.00 weight % sodium carboxymethyl cellulose.

In certain embodiments the composition comprises one or more humectants.Humectants can prevent the composition from hardening upon exposure toair. In certain embodiments the composition comprises one or morehumectants selected from edible polyhydric alcohols such as glycerine,sorbitol, xylitol, propylene glycol and mixtures thereof. In certainembodiments the composition comprises from about 5 to about 25%humectant. In certain embodiments the composition comprise from about 5to about 25% glycerine.

The compositions of the invention can be used to protect teeth byfacilitating repair and remineralization. In particular the compositionsof the invention can be used reduce or inhibit formation of dentalcaries, reduce, repair or inhibit pre-carious lesions of the enamel,reduce or inhibit demineralization and promote remineralization of theteeth, reduce hypersensitivity of the teeth, reduce or inhibitgingivitis, promote healing of sores or cuts in the oral cavity, reducelevels of acid producing bacteria, increase relative levels ofarginolytic bacteria, reduce or inhibit microbial biofilm formation inthe oral cavity, reduce or inhibit plaque formation in the oral cavity,promote systemic health, clean teeth and oral cavity.

In certain embodiments, the compositions of the invention can be used inmethods to enhance oral health and thereby provide benefits in systemichealth. Good oral health is associated with systemic health includingcardiovascular health. Basic amino acids, especially arginine, aresources of nitrogen which NO synthesis pathways and thus enhancemicrocirculation in the oral tissues. Providing a less acidic oralenvironment is also helpful in reducing gastric distress and creates anenvironment less favourable to Heliobacter which is associated withgastric ulcers. Arginine in particular is required for high expressionof specific immune cell receptors, for example T-cell receptors, so thatarginine can enhance an effective immune response. The compositions andmethods of the invention are thus useful to enhance systemic health,including cardiovascular health.

In certain embodiments of the invention, the composition is applied tothe oral cavity using a manual or electric toothbrush.

In certain embodiments, the composition is applied to the oral cavity ofa mammal. In certain embodiments the composition is applied to the oralcavity of a juvenile mammal. In certain embodiments the composition isapplied to the oral cavity of a human subject under the age of 18 years.

The compositions of the invention can provide excellent anti-cavityprotection whilst also possessing good stability and product integrity.

Examples

A dentifrice composition Formulation A according to Table 1 wasprepared:

TABLE 1 Formulation A INGREDIENT WEIGHT % Purified water and colour 33.7Glycerin 16.1 Sodium carboxymethylcellulose 1.04 Sodium saccharin 0.40Sodium hydroxide 50% 0.10 Sodium monofluorophosphate 1.10 Tetrasodiumpyrophosphate 0.50 Benzyl alcohol 0.50 Sodium bicarbonate 0.50Precipitated calcium carbonate 41.0 Sodium lauryl sulfate 95% 1.85Arginine bicarbonate 2.67 Flavor (41% menthol) 0.50

This formulation was found to suffer from phase separation and to lackstability. Formulation A was subjected to an ageing stability study. Theformulation was stored in a laminate container under various conditionsand assessed at various time points for viscosity and appearance(whiteness). Appearance was assessed on a scale of whiteness from 0(worst) to 4 (best). The results are shown in Table 2:

TABLE 2 Time Viscosity Appearance Conditions (weeks) (×10,000 cps) (0-4)−30° C.  8 — FAIL (1) 25° C. 0 25 PASS (4)  60% relative humidity 25° C.4 CANCELLED PASS (2)  60% relative humidity 25° C. 8 CANCELLED FAIL (1)60% relative humidity 25° C. 13 CANCELLED FAIL (1) 60% relative humidity40° C. 4 CANCELLED FAIL (1) 75% relative humidity 40° C. 8 CANCELLEDFAIL (1) 75% relative humidity 40° C. 13 CANCELLED FAIL (1) 75% relativehumidity

Viscosity is measured using a Brookfield Viscometer (RVT or RVTDV) atcontrolled room temperature (75-77° F./24-25° C.) using T-E spindle at 5rpm. Readings are converted to viscosity in centipoise by multiplying by10,000 for T-E spindle at 5 rpm.

A dentifrice composition Formulation B according to the presentinvention was prepared. This formulation is provided in Table 3:

TABLE 3 Formulation B INGREDIENT WEIGHT % Purified water and colour 34.6Glycerin 16.1 Sodium carboxymethylcellulose 0.80 Sodium saccharin 0.40Sodium hydroxide 50% 0.10 Sodium monofluorophosphate 1.10 Tetrasodiumpyrophosphate 0.50 Benzyl alcohol 0.50 Sodium bicarbonate 0.50Precipitated calcium carbonate 41.0 Sodium lauryl sulfate 95% 1.20Arginine bicarbonate 2.67 Flavor (41% menthol) 0.50

Formulation B was found to possess excellent formulation properties withgood structure and no oily separation. This contrasts with formulationscomprising an increased level of sodium lauryl sulfate of 1.75 or 1.80weight % which were observed to suffer from oily separation.

Formulation B was also subjected to an ageing stability study. Theformulation was stored in a laminate container under various conditionsand assessed at various time points for viscosity and appearance(whiteness). Once again appearance was assessed on a scale of whitenessfrom 0 (worst) to 4 (best). The results are shown in Table 4:

TABLE 4 Time Viscosity Appearance Conditions (weeks) (×10,000 cps) (0-4)−30° C.  8 — PASS (4) 25° C. 0 30 PASS (4) 60% relative humidity 25° C.4 48 PASS (4) 60% relative humidity 25° C. 8 53 PASS (4) 60% relativehumidity 25° C. 13 64 PASS (4) 60% relative humidity 40° C. 4 53 PASS(3) 75% relative humidity 40° C. 8 67 PASS (4) 75% relative humidity 40°C. 13 62 PASS (4) 75% relative humidity

Viscosity is measured using a Brookfield Viscometer (RVT or RVTDV) atcontrolled room temperature (75-77° F./24-25° C.) using T-E spindle at 5rpm. Readings are converted to viscosity in centipoise by multiplying by10,000 for T-E spindle at 5 rpm.

The stability of Formulation B was also compared to Formulation Ccomprising a similar level of sodium carboxymethyl cellulose, but ahigher level of sodium lauryl sulfate.

TABLE 5 Formulation C INGREDIENT WEIGHT % Purified water and colour34.22 Glycerin 16.1 Sodium carboxymethylcellulose 0.60 Sodium saccharin0.4 Sodium hydroxide 50% 0.1 Sodium monofluorophosphate 1.1 Tetrasodiumpyrophosphate 0.5 Benzyl alcohol 0.5 Sodium bicarbonate 0.5 Precipitatedcalcium carbonate 41 Sodium lauryl sulfate 95% 1.81 Arginine bicarbonate2.67 Flavor (41% menthol) 0.50

Formulation C was subjected to an ageing stability study. As before, theformulation was stored in a laminate container under various conditionsand assessed at various time points for viscosity and appearance(whiteness). Once again appearance was assessed on a scale of whitenessfrom 0 (worst) to 4 (best). The results are shown in Table 6:

TABLE 6 Time Viscosity Appearance Conditions (weeks) (×10,000 cps) (0-4)25° C. 0   23.3 PASS (4)  60% relative humidity 25° C. 4 38 PASS (3) 60% relative humidity 25° C. 8 N/A FAIL (1) 60% relative humidity 25° C.13 CANCELLED CANCELLED 60% relative humidity 40° C. 4 33 PASS (3)  75%relative humidity 40° C. 8 N/A FAIL (1) 75% relative humidity 40° C. 13CANCELLED CANCELLED 75% relative humidity 49° C. 4 N/A PASS (3)  49° C.6 CANCELLED CANCELLED 49° C. 8 N/A FAIL (1) 49° C. 13 CANCELLEDCANCELLED  4° C. 4 N/A  PASS(3)  4° C. 8 N/A FAIL (1)  4° C. 13 N/ACANCELLED

Viscosity is measured using a Brookfield Viscometer (RVT or RVTDV) atcontrolled room temperature (75-77° F./24-25° C.) using T-E spindle at 5rpm. Readings are converted to viscosity in centipoise by multiplying by10,000 for T-E spindle at 5 rpm.

The results of this ageing stability study show that this formulationalso suffers from phase separation and lacks stability.

What is claimed is:
 1. An oral care composition comprising (i) basicamino acid in free or salt form, (ii) calcium carbonate, (iii) afluoride ion source, wherein the fluoride source comprises sodiummonofluorophosphate from about 0.5 to about 2.0 weight %, (iv) aflavoring agent comprising less than 50% menthol and (v) an anionicsurfactant, wherein the anionic surfactant is present in an amount from1.00 weight % to 1.39 weight %.
 2. The oral care composition of claim 1further comprising a bacteriostatic preservative.
 3. The oral carecomposition of claim 1 further comprising benzyl alcohol.
 4. The oralcare composition of claim 1 further comprising 0.25 weight % to 0.75weight % benzyl alcohol.
 5. The oral care composition of claim 1 whereinthe calcium carbonate is precipitated calcium carbonate.
 6. The oralcare composition of claim 1 wherein the composition comprises from 20weight % to 60 weight % calcium carbonate.
 7. The oral care compositionof claim 1 wherein the anionic surfactant is a water-soluble salt of aC₁₀ to C₁₈ alkyl sulfate.
 8. The oral care composition of claim 1wherein the anionic surfactant is sodium lauryl sulfate.
 9. The oralcare composition of claim 1 wherein the composition comprises 1.05weight % to 1.30 weight % sodium lauryl sulfate.
 10. The oral carecomposition of claim 1 wherein the flavoring agent comprises less than45% menthol.
 11. The oral care composition of claim 1 wherein thecomposition comprises 0.1 weight % to 2.0% flavoring agent.
 12. The oralcare composition of claim 1 wherein the composition comprises 0.90weight % to 1.30 weight % sodium monofluorophosphate.
 13. The oral carecomposition of claim 1 wherein the composition comprises a basic aminoacid selected from one or more of arginine, lysine, histidine,citrulline, ornithine, creatine, diaminobutanoic acid, diaminoproprionicacid, and salts and combinations thereof.
 14. The oral care compositionof claim 1 wherein the composition comprises a basic amino acid selectedfrom arginine, citrulline, ornithine and salts and combinations thereof.15. The oral care composition of claim 1 wherein the compositioncomprises L-arginine or a salt thereof.
 16. The oral care composition ofclaim 1 wherein the composition comprises 1.0 weight % to 5.0 weight %of a basic amino acid or salt thereof.
 17. The oral care composition ofclaim 1 wherein the composition comprises 1.5 weight % to 3.5 weight %L-arginine bicarbonate.
 18. The oral care composition of claim 1 whereinthe composition comprises (i) 1.0 to 5.0 weight % of a basic amino acidin free or salt form (ii) 38 weight % to 44 weight % precipitatedcalcium carbonate (iii) 0.90 weight % to 1.30 weight % sodiummonofluorophosphate (iv) 0.25 weight % to 1.0% flavoring agentcomprising less than 50% menthol (v) 1.05 weight % to 1.30 weight %sodium lauryl sulfate.
 19. The oral care composition of claim 1 whereinthe composition comprises (i) 1.0 to 5.0 weight % of a basic amino acidin free or salt form (ii) 38 weight % to 44 weight % precipitatedcalcium carbonate (iii) 0.90 weight % to 1.30 weight % sodiummonofluorophosphate (iv) 0.25 weight % to 1.0% flavoring agentcomprising less than 50% menthol (v) 1.05 weight % to 1.30 weight %sodium lauryl sulfate (vi) 0.65 weight % to 1.00 weight % sodiumcarboxymethylcellulose.
 20. The oral care composition of claim 1 whereinthe composition is a dentifrice.
 21. The oral care composition of claim1 wherein the composition is a toothpaste or gel.
 22. A method to (i)reduce or inhibit formation of dental caries, (ii) reduce, repair orinhibit pre-carious lesions of the enamel, (iii) reduce or inhibitdemineralization and promote remineralization of the teeth, (iv) reducehypersensitivity of the teeth, (v) reduce or inhibit gingivitis, (vi)promote healing of sores or cuts in the oral cavity, (vii) reduce levelsof acid producing bacteria, (viii) increase relative levels ofarginolytic bacteria, (ix) reduce or inhibit microbial biofilm formationin the oral cavity, (x) reduce or inhibit plaque formation in the oralcavity, (xi) promote systemic health, (xii) clean teeth and oral cavity,comprising applying an effective amount of an oral care compositionaccording to claim 1 to the oral cavity of a subject in need thereof.23. The method of claim 22 wherein the subject is a mammal.
 24. Themethod of claim 22 wherein the subject is a juvenile.
 25. An oral carecomposition according to claim 1 for use in a method to i) reduce orinhibit formation of dental caries, ii) reduce, repair or inhibitpre-carious lesions of the enamel, iii) reduce or inhibitdemineralization and promote remineralization of the teeth, iv) reducehypersensitivity of the teeth, v) reduce or inhibit gingivitis, vi)promote healing of sores or cuts in the oral cavity, vii) reduce levelsof acid producing bacteria, viii) increase relative levels ofarginolytic bacteria, ix) reduce or inhibit microbial biofilm formationin the oral cavity, x) reduce or inhibit plaque formation in the oralcavity, xi) promote systemic health, xii) clean teeth and oral cavity.26. A method for preparing an oral care composition according to claim 1comprising the sequential steps of (i) adding the basic amino acid to asolution comprising the fluoride ion source, (ii) adding the calciumcarbonate, (iii) adding the anionic surfactant.